Emma C. Morris, United Kingdom
University College London Institute of Immunity & TransplantationPresenter of 3 Presentations
IMMUNE EVASION AND RESISTANCE TO CANCER IMMUNOTHERAPIES: LESSONS FROM T CELL FUNCTIONAL DEFECTS
PRIOR MALIGNANCY DOES NOT CONFER INFERIOR OUTCOMES IN TEENAGERS AND ADULTS WITH PRIMARY IMMUNODEFICIENCIES UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION.
Abstract
Background and Aims
Primary immunodeficiency disorders (PIDs) result in recurrent infections and a predisposition to malignancy due to impaired immune surveillance.1Large registry studies have demonstrated a 1.42-fold excess relative risk of malignancy, with lymphoproliferative disorders the most common.2Allogeneic haematopoietic stem cell transplantation (alloHSCT) is the only curative option for most PIDs.3Recently, reduced intensity conditioned alloHSCT has been shown to be effective and safe in adults with PID.4,5PID associated malignancy is often a trigger for alloHSCT in adult PID patients.
Methods
Evidence from the paediatric population suggests the presence of malignancy in PID patients should not preclude alloHSCT.6 There is scant data on alloHSCT outcome in adult PID patients with a history of malignancy. We compared overall survival (OS) between patients with a history of a malignancy (n= 12) and those without (n=35) in our cohort of (n=47) teenagers and young adults (aged >13, median 22) with PID (Fig 1). The patients in the malignant group had haematological (6 MDS, 3 Hodgkin Lymphoma, 1 B-cell NHL, 1 T-cell NHL, 1 autoimmune lymphoproliferative disorder) and epithelial malignancies (2 VIN/CIN/AIN and 1 poorly differentiated squamous cell carcinoma). Patients with lymphoma were in remission prior to transplant.
Results
OS in the patients with malignancy was 100% (median follow up 4 years) with no recurrence of malignancy post-transplant(vs 82.9% in the non-malignant group, p=0.147).
Conclusions
AlloHSCT may be particularly useful in adult patients with PID-associated malignancy as the restoration of immune surveillance and provision of a life-long graft-vs-tumour effect may reverse the inherited predisposition to malignancy.
DISSEMINATED EBV-ASSOCIATED LEIOMYOMAS AS A NOVEL PRESENTING FEATURE OF DOMINANT NEGATIVE CARD11 MUTATION ASSOCIATED PRIMARY IMMUNODEFICIENCY IN ADULTHOOD.
Abstract
Background and Aims
Background and Aims: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to NFκB, c-Jun N-terminal kinase, and mTORC1. This case report describes the unusual clinical presentation of an adult with a dominant negative (DN) monoallelic mutation in CARD11.
Methods
Methods: Analysis of medical records, laboratory results, tissue biopsies and gene sequencing information.
Results
Results: Our patient was referred to us for the consideration of allogeneic HSCT at the age of 40 years. His history dated back to childhood with early onset atopy, multiple food allergies and eczema. At the age of 29 years he presented with multiple intrathoracic and hepatic tumours, which on biopsy were shown to be EBV-associated leiomyomas. Immunology investigations demonstrated a mild reduction in B cells with normal total T and NK cells, preserved immunoglobulin levels but a suboptimal response to polysaccharide pneumococcal vaccine. Targeted chip sequencing identified a previously described monoallelic missense mutation (c.214C>G; NM_032415.4:c.214C>G, R72G) with dominant negative effect. The previous cases were characterised in two patients by alopecia, joint pain, oral ulcers, pulmonary TB; and in a third by persistent skin infections (VZV, HPV), EBV viremia, progressive B-cell lymphopenia and frequent osteomyelitis.
Conclusions
Conclusion: EBV-associated leiomyomas are a rare complication of PID, described in less than 20 cases to date with a range of underlying genetic causes. To our knowledge, this is the first case of EBV leiomyomatosis in CARD11 related PID and expands the spectrum of clinical phenotype of CARD11 mutations.